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The Immune System in Multiple Myeloma

Sponsor: Scientific Committee on Plasma Cell Neoplasia
Program: Scientific Program
Hematology Disease Topics & Pathways:
Biological, multiple myeloma, Diseases, smoldering myeloma, Therapies, Biological Processes, Technology and Procedures, immunotherapy, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant, genomics, NGS
Monday, December 7, 2020: 11:25 AM-11:30 AM

Description:
The Immune System in Multiple Myeloma

The immune repertoire plays an important role in many cancers, and there has been growing recognition of the immune deregulation plays an important and independent role in the progression of malignant plasma cells through the precursor states to active disease. The progression of multiple myeloma is associated with both innate and adaptive immune system dysfunction, notably in the T-cell repertoire Understanding the interplay between the bone marrow microenvironment, immune repertoire and malignant plasma cells will be of utmost important to achieve long-term disease control and potential curability.

Dr. Kyohei Nakamura will discuss the immune system as it related to the progression of the precursor condition MGUS to active myeloma. His lab has been exploring the relative importance of different immune cells and molecules in blood cancers, from their initiation, growth and spread and under therapy. To that end, his research has demonstrated that the pro-inflammatory cytokine IL-18 is critically involved in these hallmarks in multiple myeloma (MM). In addition, blocking TIGIT using monoclonal antibodies (mAbs) increased the effector function of MM patient CD8+ T cells and suppressed MM development. Furthermore, besides examining the role of extracellular adenosine in blood cancers, Dr. Nakamura is now also evaluating models of minimal residual disease as a treatment window of opportunity for MM.

Dr. Paola Neri will discuss insights into the mechanisms that promote tumor escape, cause inadequate T-cell stimulation and impaired cytotoxicity in MM. In addition, she will highlight current immunotherapies being used to restore adaptive T-cell immune responses in MM and describe strategies created to escape these multiple immune evasion mechanisms. Her lab been examining the complex interaction of BM stromal cells (BMSCs) and malignant cells that using bidirectional connections and cytokines released stimulate disease progression, drug resistance and enable immune escape, showing distinct immunophenotyping features using single cell RNA sequencing and mass spectrometry.

Dr. Madhav Dhodapkar will discuss emerging data from studies to evaluate the immune system in myeloma patients receiving therapy. He will be discussion the potential immune signatures in response to therapy in newly diagnosed and relapsed myeloma patients, as the efficacy of T-cell-dependent immunotherapies for myeloma are going to depend on engaging the endogenous T-cell repertoire. He will discuss the potential applications of different immune monitoring approaches that are providing novel insights for strategies to harness the immune system to treat myeloma.

Chair:
Saad Z. Usmani, MD, MBBS, MBA, Levine Cancer Institute
Disclosures:
Usmani: Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Incyte: Research Funding; Merck: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; SkylineDX: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Seattle Genetics: Consultancy, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Pharmacyclics: Research Funding.
The Immune System in Multiple Myeloma

The immune repertoire plays an important role in many cancers, and there has been growing recognition of the immune deregulation plays an important and independent role in the progression of malignant plasma cells through the precursor states to active disease. The progression of multiple myeloma is associated with both innate and adaptive immune system dysfunction, notably in the T-cell repertoire Understanding the interplay between the bone marrow microenvironment, immune repertoire and malignant plasma cells will be of utmost important to achieve long-term disease control and potential curability.

Dr. Kyohei Nakamura will discuss the immune system as it related to the progression of the precursor condition MGUS to active myeloma. His lab has been exploring the relative importance of different immune cells and molecules in blood cancers, from their initiation, growth and spread and under therapy. To that end, his research has demonstrated that the pro-inflammatory cytokine IL-18 is critically involved in these hallmarks in multiple myeloma (MM). In addition, blocking TIGIT using monoclonal antibodies (mAbs) increased the effector function of MM patient CD8+ T cells and suppressed MM development. Furthermore, besides examining the role of extracellular adenosine in blood cancers, Dr. Nakamura is now also evaluating models of minimal residual disease as a treatment window of opportunity for MM.

Dr. Paola Neri will discuss insights into the mechanisms that promote tumor escape, cause inadequate T-cell stimulation and impaired cytotoxicity in MM. In addition, she will highlight current immunotherapies being used to restore adaptive T-cell immune responses in MM and describe strategies created to escape these multiple immune evasion mechanisms. Her lab been examining the complex interaction of BM stromal cells (BMSCs) and malignant cells that using bidirectional connections and cytokines released stimulate disease progression, drug resistance and enable immune escape, showing distinct immunophenotyping features using single cell RNA sequencing and mass spectrometry.

Dr. Madhav Dhodapkar will discuss emerging data from studies to evaluate the immune system in myeloma patients receiving therapy. He will be discussion the potential immune signatures in response to therapy in newly diagnosed and relapsed myeloma patients, as the efficacy of T-cell-dependent immunotherapies for myeloma are going to depend on engaging the endogenous T-cell repertoire. He will discuss the potential applications of different immune monitoring approaches that are providing novel insights for strategies to harness the immune system to treat myeloma.

Kyohei Nakamura, MD, PhD

QIMR Berghofer Medical Research Institute, Herston, Australia

Paola Neri, MD

University of Calgary, Calgary, AB, Canada

Madhav V. Dhodapkar, MBBS

Emory University, Atlanta, GA

See more of: Scientific Program